Oxytocin levels in the posterior pituitary and in the heart are modified by voluntary wheel running

We hypothesized that voluntary wheel running results in increased secretion of oxytocin, a peptide involved in the stress response. An additional hypothesis was that prolonged exercise affects oxytocin levels in the heart, which is in line with the potential role of oxytocin in cardiovascular functions. Voluntary wheel running lasted 3 weeks and daily running distances increased progressively reaching maximum levels about 8 km (Sprague-Dawley rats) and 4 km (Lewis strain). The exercise resulted in significant reduction of epididymal fat, slight increase in glucose transporter GLUT4 mRNA levels and significant enhancement of plasma density. Voluntary exercise failed to influence plasma oxytocin levels either in Lewis or Sprague-Dawley rats, but it resulted in a significant decrease of oxytocin concentrations in the posterior pituitary. Plasma oxytocin concentrations were not modified even if the measurements were made in the dark phase of the day. In voluntary wheel running Sprague-Dawley rats, the content of oxytocin in the right heart atrium was lower than in controls. Thus, the present findings demonstrate that prolonged voluntary wheel running results in a decrease in pituitary oxytocin content without evident changes in hormone concentrations in peripheral blood. However, prolonged exercise used has a significant impact on oxytocin levels in the heart.     

Genetic differences in Δ9-tetrahydrocannabinol-induced facilitation of brain stimulation reward as measured by a rate-frequency curve-shift electrical brain stimulation paradigm in three different rat strains

Lewis, Fischer 344, and Sprague-Dawley rats were implanted with electrodes in the medial forebrain bundle and trained to lever press for brain stimulation reward using a ratefrequency curve-shift electrical brain stimulation paradigm based on a series of 16 pulse frequencies ranging from 25 to 141 Hz in descending order. Once reward thresholds were stable, rats were given 1.0 mg/kg Δ⁹-tetrahydrocannabinol (Δ⁹-THC), the psychoactive constituent in marijuana and hashish, or vehicle, by intraperitoneal injection. Lewis rats showed the most pronounced Δ⁹-THC-induced enhancement of brain reward functions. Sprague-Dawley rats showed an enhancement of brain reward functions that was approximately half that seen in Lewis rats. Brain reward functions in Fischer 344 rats were unaffected by Δ⁹-THC at the dose tested. These results are consistent with previous work showing Lewis rats to be highly sensitive to the rewarding properties of a variety of drugs of abuse, including opiates, cocaine, and alcohol, while Fischer 344 rats are relatively less sensitive. They extend such previous findings to cannabinoids, and further suggest that genetic variations to other cannabinoid effects may also exist.     

Age-related differences in the cardiovascular responses to haemorrhagic shock in rats.

The cardiovascular responses to haemorrhagic shock were studied in male Sprague-Dawley rats of different age groups, ranging from 6-15 weeks (body weight 250-460 g). Haemorrhagic shock was induced by bleeding (2% body weight), under urethane anaesthesia, from the cannulated femoral artery at a rate of 1 ml/min. It was found that the younger rats had significantly smaller values of left ventricular pressure and dLVP/dtmax following haemorrhage and a greater mortality rate. Older animals exhibited significantly greater falls in blood pressure and pulse rate during the bleeding procedure, and slower recovery in these parameters after the bleeding was stopped. However, these rats had a significantly higher left ventricular pressure and dLVP/dtmax following haemorrhage, and a markedly lower mortality rate. The findings demonstrate the existence of age-related cardiovascular responses to haemorrhagic shock in rats.     

三种正常大鼠磁共振成像心功能基础数据采集和分析

目的大鼠是常用的制备心脏病模型的实验动物,而磁共振成像（MRI）技术已经成为评价心脏病模型病理进程和药效的重要技术手段,但是目前国内外没有正常大鼠心脏的磁共振成像技术参数,影响了这一技术的应用。本文利用磁共振成像技术,采集和定量分析Wistar、Sprague-Dawley和Lewis三种常用大鼠的左、右心室功能参数,为心脏病模型制备和分析提供参考数据。方法利用7．0T高场强MRI心脏电影（CINE）序列,分析这三种常用大鼠活体心脏组织的左、右心室心功能参数。结果获得三种大鼠左、右心室的8—9周龄功能参数,包括：左、右心室的舒张末容积（EDV）、收缩末容积（ESV）、射血分数（EF）;左心室乳头肌层面舒张末期内径（EDD）、收缩末期内径（ESD）、短轴缩短率（Fs）、舒张末前后室壁厚度（EDAWT,EDPWT）、收缩末前后室壁厚度（ESAWT,ESPWT）、前室壁增厚率（AWT）和后室壁增厚率（PwT）;右心室乳头肌层面舒张末室壁厚度（EDWT）、收缩末室壁厚度（ESWT）和室壁增厚率（WT）等十八项心脏主要功能和结构的正常值。结论本研究获得的三种大鼠十八项心脏主要功能和结构的正常值,可作为心脏病模型制备成模判定和病理进程、药物评价的参考数据。     

Detection of surface differences between two closely related cell populations by partitioning. Erythrocytes from inbred and out-bred rats and rat strains

We have recently developed a new and powerful method capable of detecting, by purely physical means, surface differences between closely related red (or other) cell populations. The procedure consists of isotopically labeling (with [⁵¹Cr]chromate) aliquots of red blood cell populations. Such labeled cells are mixed with an excess of unlabeled red cells to which they are to be compared. The mixtures are subjected to countercurrent distribution in either a charge-sensitive or a non-charge-sensitive dextran-poly(ethylene glycol) aqueous phase system. The distribution curves are analyzed for total cells (in terms of hemoglobin absorbance) and labeled cells (in terms of cpm). Changes in the relative specific activities through the distribution curves are indicative of subtle differences in surface properties between such cell populations. Using this method we have found that erythrocytes from arbitrarily chosen (presumably hematologically normal) individuals differ. In the current work we have examined the surface properties of erythrocytes from Sprague-Dawley and from Lewis rats. This was done with a view to determining whether (a) differences of the type found between different humans can also be detected in other species and (b), if such differences do exist, to examine, by study of the highly inbred Lewis rat strain, whether the differences appear to have a genetic or an acquired basis. It was found that the surface properties of erythrocytes from Lewis and Sprague-Dawley rats differ as do erythrocytes among rats of the Sprague-Dawley strain. No difference was found between red blood cells from different rats of the inbred Lewis strain. These results indicate that the surface differences between red blood cells from different rats detected by partitioning have a genetic rather than acquired origin.     

Age-related cardiovascular responses of rats to coronary artery ligation

The cardiovascular responses of rats of different ages, ranging from 4-15 weeks (body weight 115-490 g), to acute left coronary artery ligation under pentobarbitone anaesthesia were studied. In older animals, the responses included the occurrence of ventricular tachycardia and/or fibrillation, decrease in blood pressure, and a slight increase in heart rate. On the contrary, younger rats exhibited atrioventricular block followed by ventricular arrest, and decreases in both blood pressure and heart rate. The findings demonstrate the existence of age-related cardiovascular responses to acute myocardial ischaemia in rats, and suggest that 10-15-week-old male Sprague-Dawley rats are suitable experimental animals for producing early ventricular arrhythmias by acute coronary artery ligation.     

Development of an animal model for investigating disparate myocardial effects of obesity and hypertension

An experimental model for investigating the disparate effects of obesity and hypertension on the heart was developed by ligation of the aorta of male Sprague-Dawley rats made obese through ad libitum feeding. Experimental obesity was associated with an increased body fat and cardiac muscle mass, yet a normotensive systemic arterial pressure. Aortic ligation produced an elevated mean arterial pressure and resting heart rate, whereas body weight was similar to that of normotensive lean control rats. Obesity and hypertension together were associated with a significantly increased percent body fat, mean arterial pressure, and left ventricular mass compared with lean controls, whereas pressure and left ventricular weight were greater than those observed in rats with only obesity or hypertension. Cardiac adaptations corrected for body weight indicated that left ventricular weight increased as a function of body weight and body fat, but hypertension produced left ventricular adaptations independent of these variables. These initial studies indicate an additional contribution of hypertension to the left ventricular adaptations of obesity, and this model could therefore be used in future investigations concerning the cardiovascular effects of the simultaneous occurrence of these separate diseases.     

The influence of vasovasostomy on antisperm antibodies in rats

Serum antisperm antibodies were studied in Sprague-Dawley rats after vasectomy and vasovasostomy. Animals received a bilateral vasectomy, a vasectomy followed 3 mo later by vasovasostomy, or sham operations. Blood samples were obtained at 1, 3, 4, and 7 mo, and antisperm antibodies were assayed by an enzyme-linked immunosorbent assay. After vasectomy reversal was performed at 3 mo, antisperm antibodies were significantly higher in rats in the vasovasostomy group at 4 mo than in animals that had a persisting vasectomy or sham operations. At 7 mo, the antisperm antibody level for the vasovasostomy group was approximately double that for the vasectomized rats. Spermatic granulomas occurred in 76% of rats after vasovasostomy. Antisperm antibody levels were higher in vasovasostomized animals with granulomas than in those lacking granulomas. The results suggest that vasovasostomy may stimulate an antibody response to sperm rather than lead to a reduced response, as was anticipated upon removal of the obstruction. Spermatic granulomas may serve as sires for continued antigenic challenge. The observed increase in antisperm antibodies after vasovasostomy in Sprague-Dawley rats may be related to their relatively low immunologic responsiveness to vasectomy, with vasovasostomy serving as a second major immunologic challenge, aided by the formation of an additional granuloma. In the more responsive Lewis strain, we previously observed a rise in antisperm antibodies after the initial vasectomy, with no further increase after vasovasostomy.     

Cardiovascular dysfunction in Zucker obese and Zucker diabetic fatty rats: role of hydronephrosis

Recent studies in our laboratory using the Zucker obese (ZO) and Zucker diabetic fatty (ZDF) rat models resulted in unexpectedly high mortality rates in all genotypes including healthy homozygous lean Zucker rats, possibly because of renal dysfunction. Therefore, we evaluated left ventricular (LV) and kidney morphology and function in young ZO, Zucker diabetic fatty obese (ZDFO), homozygous Zucker/ZDF lean (ZL), and Sprague-Dawley (SD) rats. Hydronephrosis was evident in ZL, ZO, and ZDFO but not SD kidneys. ZDFO rats exhibited impaired LV shortening and relaxation with increased arterial stiffness. LV wall thickness was lower and LV end-systolic wall stress was higher in ZDFO compared with SD rats. Plasma ANG II was lower in ZO and ZDFO rats, which may be a result of reduced renal parenchyma with hydronephrosis; norepinephrine was higher in ZDFO rats than SD controls. Covariate analysis indicated that LV end-systolic wall stress was associated with renal dysfunction. The presence of hydronephrosis and its association with LV dysfunction potentially limits the ZDF model for study of the effects of diabetes on renal and cardiovascular function.     

Direct delivery of syngeneic and allogeneic large-scale expanded multipotent adult progenitor cells improves cardiac function after myocardial infarct

BACKGROUND: Multipotent adult progenitor cells (MAPC) comprise interesting candidates for myocardial regeneration because of a broad differentiation ability and immune privilege. We aimed to compare the improvement of cardiac function by syngeneic and allogeneic MAPC produced on a large scale using a platform optimized from MAPC research protocols. METHODS: Myocardial infarction was induced in Lewis rats by direct left anterior descending ligation followed immediately by direct injection into the infarct border zone of either Sprague-Dawley or Lewis MAPC from large-scale expansions. Echocardiography was performed to evaluate improvement in cardiac function, and immunohistochemistry was performed to identify MAPC within the infarct zone. RESULTS: Significant increases were observed in functional performance in animals transplanted with expanded MAPC compared with saline controls, with no significant differences between the syngeneic and allogeneic groups. Immunostaining demonstrated significant engraftment of expanded MAPC at 1 day after acute myocardial infarction, with <10% of either syngeneic or allogeneic cells remaining at 6 weeks. At this point there was no evidence of myocardial regeneration. However, a significant increase in vascular density within the infarct zone in MAPC-transplanted animals was observed, and MAPC were found to produce high levels of VEGF in culture. DISCUSSION: These findings support a model in which delivery of expanded MAPC following acute myocardial infarction results in improvement in cardiac function because of paracrine effects resulting in vascular density increases, as well as potentially other trophic effects, supporting newly injured cardiac myocytes. Thus transplantation with MAPC may represent a promising therapeutic strategy with application in the stimulation of neovascularization in ischemic heart disease.     

Abnormal Igf2 gene in Prague hereditary hypertriglyceridemic rats: its relation to blood pressure and plasma lipids

Prague hypertriglyceridemic (HTG) rats represent a suitable model of metabolic syndrome. We have established the set of F(2) hybrids derived from HTG and Lewis progenitors to investigate the relationship between respective polymorphism(s) of Igf2 gene and blood pressure (BP) or other cardiovascular phenotypes. HTG rats had elevated systolic BP and plasma triglycerides but lower plasma cholesterol compared to Lewis rats of both genders. In males, there was higher mean arterial pressure, diastolic BP and relative heart weight in HTG than in Lewis rats. The results obtained in the total population of F(2) hybrids indicated strong segregation of Igf2 genotype with plasma triglycerides. There was no segregation of Igf2 genotype with any BP component except BP changes occurring after the blockade of either renin-angiotensin system (RAS) or NO synthase. When F(2) population was analyzed according to gender, male F(2) progeny homozygous for HTG Igf2 allele had significantly higher plasma triglycerides and greater BP changes after NO synthase blockade than those homozygous for Lewis allele. On the contrary, male F(2) progeny homozygous for HTG Igf2 allele had significantly lower plasma cholesterol and smaller BP changes after RAS blockade. PCR analysis of Igf2 gene by using of microsatelite D1Mgh22 has shown polymorphism between HTG and Lewis rats. Sequence analysis of cDNA revealed insertion of 14 nucleotides in HTG gene. In conclusion, polymorphism in Igf2 gene may be responsible for differences in lipid metabolism between HTG and Lewis rats. It remains to determine how these abnormalities could be involved in BP regulation by particular vasoactive systems.     

Glial Fibrillary Acidic Protein and the Mesolimbic Dopamine System: Regulation by Chronic Morphine and Lewis-Fischer Strain Differences in the Rat Ventral Tegmental Area

Abstract— In this study we demonstrate that a 51-kDa phosphoprotein, previously identified as morphine regulated and showing different basal levels among rat strains, is glial fibrillary acidic protein (GFAP). Chronic morphine increased levels of GFAP immunoreactivity by >70% in the ventral tegmental area (VTA) of outbred Sprague-Dawley rats. This increase in GFAP content was not observed in rats that were treated concomitantly with morphine and naltrexone, an opiate receptor antagonist, and did not occur in response to a single acute injection with morphine. No alterations in GFAP levels were observed in response to chronic morphine in several other regions of the CNS studied, including the substantia nigra, locus coeruleus, cerebral cortex, and spinal cord. There were also inherent differences in levels of GFAP immunoreactivity in the VTA of drug-naive Fischer 344 and Lewis rats, two inbred rat strains that differ in their relative preference for morphine and other drugs of abuse. The VTA of drug-naive Lewis rats contained more than twofold higher levels of GFAP compared with drug-naive Fischer rats. This strain difference was also apparent in the locus coeruleus but not in several other brain regions or in spinal cord. Because the mesolimbic dopamine system is thought to play a critical role in mediating the reinforcing properties of opiates and other drugs of abuse, it is possible that the opiate induction of GFAP and inherent Lewis versus Fischer strain differences in GFAP levels in the VTA may be related to the reinforcing and/or addictive properties of opiates mediated by this brain region, as well as to genetic differences in drug preference.     

Regional distribution of metallothionein, zinc, and copper in the brain of different strains of rats

The regional brain distribution of metallothionein (MT), zinc, and copper in the brain was determined in nine anatomical regions (olfactory bulb, cortex, corpus striatum, hippocampus, thalamus plus hypothalamus, pons plus medulla oblongata, cerebellum, midbrain, and white matter) and was compared between two different strains of rat (Sprague-Dawley [SD] and Lewis). No significant difference was observed in the whole-brain MT level between the two strains (17.8 ± 3.4 μg/g in SD rats and 20.3 ± 2.3 μg/g in Lewis rats). In SD rats, however, MT was more highly expressed in the white matter than in the other regions studied. In contrast, MT concentration was highest in the cortex and lowest in the olfactory bulb in Lewis rats. The MT levels in the cortex, corpus striatum, hippocampus, and thalamus plus hypothalamus were significantly lower in SD rats than in Lewis rats. In both strains, the olfactory bulb contained markedly higher levels of both zinc and copper than the other regions (27.9 ±6.8 μg/g zinc in SD rats and 27.6 ± 6.9 μg/g zinc in Lewis rats, and 5.2 ± 1.5 μg/g copper in SD rats and 11.1 ± 4.8 μg/g copper in Lewis rats). The next high-est zinc levels were seen in the hippocampus, whereas the next highest copper levels were in the corpus striatum in both SD and Lewis rats. The high levels of zinc and copper in the olfactory bulb were not accompanied by concomitant high MT concentrations. These results indicate that the strain of rat as well as the anatomical brain region should be taken into account in MT and metal distribution studies. However, the highest concentrations of zinc and copper in olfactory bulb were common to both SD and Lewis rats. The discrepancy between MT and the metal levels in olfactory bulb suggests a role for other proteins in addition to MT in the homeostatic control of zinc and copper.     

Salt-loading and simulated microgravity on baroreflex responsiveness in rats

Cardiovascular adaptations observed during exposure to microgravity results in impairment of baroreflex activity partially as a result of fluid and electrolyte shifts. The head-down tilt rat model mimics some of the physiological observations that have been made in astronauts. We examined the effects of salt-loading on baroreflex activity after 7 day simulated microgravity (30 degrees tail-suspension) and the subsequent 6 hr post-suspension in Sprague-Dawley (SD) rats, using low salt (0.3% NaCl) and high salt (8% NaCl) diets. In suspended animals on a low salt diet, the baroreflex response curve was shifted to the left, while the heart rate (HR) range and MAP50 values were reduced compared to their parallel tethered, non-suspended controls. For non-suspended animals, salt-loading shifted the curve to the right with a reduced HR range. In salt-loaded, suspended animals, the curve and its parameters resemble those of non-suspended animals on a low salt diet. In summary, these data have demonstrated that a short-term (seven days) simulated weightlessness may elicit cardiovascular deconditioning in rats after release from the simulation manifested as an altered responsiveness in baroreceptor-heart rate reflex and a lowered blood pressure while the rats are tethered and horizontal. Our results also suggest the counteracting effect of salt loading on cardiovascular deconditioning.     

Cardiovascular effects of prorenin blockade in genetically spontaneously hypertensive rats on normal and high-salt diet

Recent reports have demonstrated a potential role of tissue prorenin in the pathogenesis of cardiovascular and renal damage. This study was designed to examine the role of prorenin in the pathogenesis of target organ damage in spontaneously hypertensive rats (SHRs), the best naturally occurring experimental model of essential hypertension. To this end, we studied 20-wk-old male SHRs receiving a normal diet and 8-wk-old male SHRs given food with 8% NaCl. One-half the rats in each group were given prorenin inhibitor (PRAM-1, 0.1 mg.kg(-1).day(-1)) via osmotic minipumps; the other half served as controls. Arterial pressure, left ventricular function, cardiovascular mass indexes, cardiac fibrosis, and renal function were examined at the end of the experiment. Arterial pressure was unaffected by PRAM-1 in rats on either regular or salt-excess diets. In those rats receiving a normal diet, the blockade of prorenin activation consistently reduced left ventricular mass but affected no other variable. Salt-loaded rats given PRAM-1 for 8 wk demonstrated (1) reduced serum creatinine level, (2) decreased left ventricular mass, (3) improved left ventricular function, and (4) reduced left ventricular fibrosis. These data demonstrated that the blockade of nonproteolytic activation of prorenin exerted significant cardiovascular and renal benefit in SHRs with cardiovascular damage produced by salt excess and suggested that the activation of cardiovascular or renal prorenin may be a major mechanism that mediates cardiac and renal damage in this form of accelerated hypertension.     

Transient middle cerebral artery occlusion and reperfusion alters inducible NOS expression within the ventrolateral medulla and modulates cardiovascular function during static exercise

A major cause of stroke is cerebral ischemia in regions supplied by the middle cerebral artery (MCA). In this study, we hypothesized that compromised cardiovascular function during static exercise may involve altered expression of inducible NOS (iNOS) protein within the rostral ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM). We compared cardiovascular responses and iNOS protein expression within the left and right sides of both RVLM and CVLM in sham-operated rats and in rats with a 90 min left-sided MCA occlusion (MCAO) followed by 24?h of reperfusion. Increases in blood pressure during a static muscle contraction were attenuated in MCAO rats compared with sham-operated rats. Also, iNOS expression within the left RVLM was augmented compared with the right RVLM in MCAO rats and compared with both RVLM quadrants in sham-operated rats. In contrast, compared with sham-operated rats and the right CVLM of MCAO rats, iNOS expression was attenuated in the left CVLM in left-sided MCAO rats. These data suggest that the attenuation of pressor responses during static exercise in MCAO rats involves overexpression of iNOS within the ipsilateral RVLM and attenuation in iNOS within the ipsilateral CVLM. Differential expression of iNOS within the medulla plays a role in mediating cardiovascular responses during static exercise following stroke.     

Hepatic and pancreatic glycosphingolipid phenotypes of the neurological different rat strains

Among three commonly used strains of laboratory rats, Wistar rats perform more neurological tasks better then Lewis and Sprague-Dawley (SD) rats. Liver is the main site of insulin-like growth factor (IGF) production and pancreas is the exclusive site of insulin production. Insulin stimulates neuronal development and appropriate IGF-I input is critical in brain growth. Glycosphingolipids (GSLs) are important mediators of insulin secretion and action. Therefore, this study investigated GSL phenotypes of liver and pancreas with hypothesis that they are different in three rat strains. Total GSL fractions (neutral and gangliosides) were analysed by high performance thin-layer chromatography (HPTLC). Complex gangliosides were detected by HPTLC immunostaining using cholera toxin B subunit after neuraminidase pretreatment. Wistar rats had the highest liver weight/body weight ratio and SD rats had the highest pancreas weight/body weight ratio. Ganglioside GM3 was more expressed in the liver of Wistar compared to Lewis and SD rats. SD rats contained scarce quantities of GD1a and b-series gangliosides in the liver compared to Wistar and Lewis rats. Pancreatic b-series ganglioside content was also the lowest in SD rats. This study represents differences in the hepatic and pancreatic ganglioside phenotypes of three rat strains that could influence IGF and insulin secretion and action.     

Chronic treatment with dimethyl sulfoxide protects against cardiovascular defects of copper deficiency

Published reports indicate that Cu deficiency reduces antioxidant defenses and may result in tissue peroxidation. Dimethyl sulfoxide (DMSO), a highly penetrant antiinflammatory agent and purported hydroxyl radical scavenger, was chronically fed to male, weanling Sprague-Dawley rats which were either supplemented with or deficient in Cu. DMSO was found to inhibit the cardiac hypertrophy, anemia and depression of heart Cu concentration which occurs with Cu deficiency. This suggests that the hydroxyl free radical may contribute to the cardiovascular defects caused by dietary Cu deficiency.     

Reexamination of the difference in susceptibility to adjuvant-induced arthritis among LEW/Crj, Slc/Wistar/ST and Slc/SD rats.

The present investigations were performed to assess the differences among rat colonies commonly used for neurophysiological research regarding the development of complete Freund's adjuvant (CFA)-induced arthritis. Inflammatory signs including edema in the paw fluctuated remarkably among individual Wistar (Slc/Wistar/ST) and Sprague-Dawley (Slc/SD) rats, while the inflammatory signs of Lewis (LEW/Crj) rats appeared earlier and was severer and more consistent than Slc/Wistar/ST and Slc/SD rats. Edema in the hind paw developed in 100% of LEW/Crj rats with the lowest dose of CFA (0.6 mg/rat) used as compared with 64% of Slc/Wistar/ST (CFA 1 mg/rat) and 38% of Slc/SD rats (CFA 1.2 mg/rat). Retardation of weight gain was observed in Slc/Wistar/ST and Slc/SD rats in contrast to a severe weight decrease in inflamed LEW/Crj rats after the development of arthritis.     

Chronobiological serial sections for core temperature monitoring after transplantation of the murine pancreas

In order to study any early sign of rejection of pancreas transplantation, rhythmometry was carried out on female adult inbred Lewis rats. Animals previously kept in continuous light, more or less synchronized in frequency by cyclic human activities, were transferred to a regimen of light (L) and darkness (D) alternating at 12-h intervals in single cages at the room temperature of 24 +/- 1 degrees C, with food and water ad libitum. At this time under ether anesthesia, temperature transensors were implanted in healthy rats and rats rendered diabetic by the administration of streptozotocin. Some of the diabetic rats were left untreated; casual blood sampling showed gross hyperglycemia. Other rats were treated by pancreatic grafts from ethionine-prepared donors, either by isografts (in rats of the Lewis strain) or by allografts (of the pancreas from inbred Fischer rats transplanted to Lewis rats). Intraperitoneal temperature was telemetered at 10-min intervals for 3 weeks following transplantation. Urine volumes were determined from rats housed in metabolic cages. Data were analyzed rhythmometrically. Chronobiological serial sections and single cosinors served this purpose. Following sensor implantation and transfer to an LD 12:12 regimen, the adjustment of the thermal acrophase consistently near the middle of the daily dark span occurred within approximately 7 days in healthy rats and in streptozotocin-diabetic rats cured by isograft. Thermal acrophase adjustment was slower for animals rendered diabetic by streptozotocin and left untreated or for animals thus rendered diabetic which had rejected the pancreatic allograft (as documented by hyperglycemia in casually sampled blood). The eventual synchronization of the circadian temperature rhythm of allografted rats differed from one rat to the other and, for some allografted animals, from the consistent synchronization of the circadian rhythm in telemetered intraperitoneal temperature of diabetic and non-diabetic Lewis rats. The acrophase of the circadian rhythm in urine volume of healthy rats or of a rat with a pancreatic isograft (which cured a prior streptozotocin-induced diabetes) differed with statistical significance from those of rats with untreated diabetes, some in this state after the rejection of a pancreatic allograft. Both urine volume and core temperature are ready marker rhythms, not only for rats but also for human beings. Both variables can be self-monitored by the cooperation of instructed but not necessarily extensively educated patients. Temperature, in particular, can also be monitored with automatic devices and alterations of certain of its rhythm characteristics may signal changes preceding fever. The use of such admittedly unspecific yet eminently practical and possibly informative marker rhythmometry awaits clinical testing.